There is a growing body of evidence suggesting that intranasal (IN) OT modulates social cognitive processes and behaviors in humans, including increasing gaze to eye regions of others, enhancing the ability to infer the emotions of others, and increasing face recognition memory, and socially reinforced learning. These findings are remarkably consistent with rodent studies showing that OT facilitates social recognition and the formation of social bonds. The overarching hypothesis of this Conte Center application is that OT acts in animals and human subjects to increase the salience and reinforcing value of social stimuli. These findings and our overarching hypothesis have tremendous implications for the development of novel therapies for improving social function in psychiatric disorders characterized by impaired social cognition, including autism spectrum disorder (ASD) and schizophrenia. Indeed, IN-OT enhances some aspects of social functioning in patients with ASD, including increased eye-contact, improved emotion recognition and adaptive cooperation. Despite the remarkable interest in IN-OT, very little is known regarding the psychological and neural mechanisms by which OT affects social functioning in humans. We hypothesize the reported effects of INOT on complex social cognition in humans reflects an impact on the more fundamental processes of salience and reinforcing value of social stimuli. Further we hypothesize that these effects are mediated by increased activation and functional connectivity between brain regions involved in social cue perception (e.g. amygdala) and reward (e.g. ventral striatum). We will test this hypothesis using a combined approach of social cognitive tests and functional MRI (fMRI) with IN-OT administration in healthy and ASD human subjects. We hypothesize that ASD subjects will show decreased attention to social cue and decreased responses to social reinforcers than healthy subjects. The differences will be associated with differences in neural activity and connectivity. Finally IN-OT will normalize behavioral responses and neural activity in ASD subjects. If our predictions are correct, these data will have important implications for combining IN-OT and behavioral therapies to improve social function in psychiatric disorders.